What is the next step in managing a 31-year-old male with extreme dysuria (painful urination), who has tested negative for Urinary Tract Infection (UTI), Neisseria gonorrhoeae (gonorrhea), and Chlamydia trachomatis (chlamydia)?

Management of Extreme Dysuria with Negative STI Testing in a Young Male

Immediate Next Step: Confirm Nongonococcal Urethritis (NGU)

You must first document that urethritis is actually present before initiating any treatment, as empiric therapy without confirmation is only justified for high-risk patients unlikely to return for follow-up. 1

Diagnostic Confirmation Required

Urethritis can be documented by any of the following:

• Mucopurulent or purulent urethral discharge on examination 1
• Gram stain of urethral secretions showing >5 WBCs per oil immersion field (this is the preferred rapid diagnostic test) 1
• Positive leukocyte esterase test on first-void urine OR microscopic examination of first-void urine showing >10 WBCs per high power field 1

If none of these criteria are present, defer treatment and follow the patient closely. 1

Treatment Algorithm Once Urethritis is Confirmed

First-Line Treatment for NGU

Treat immediately with either azithromycin 1g orally as a single dose OR doxycycline 100mg orally twice daily for 7 days. 1

• Azithromycin is preferred for single-dose compliance and may respond better for Mycoplasma genitalium infections 1
• Doxycycline requires 7 days but is equally effective for chlamydial urethritis 1
• Provide medication directly in the clinic to ensure compliance 1

Alternative Regimens (if first-line not tolerated)

• Erythromycin base 500mg orally four times daily for 7 days 1
• Erythromycin ethylsuccinate 800mg orally four times daily for 7 days 1
• Ofloxacin 300mg orally twice daily for 7 days 1
• Levofloxacin 500mg orally once daily for 7 days 1

Understanding the Etiology

Common Causes of Nonchlamydial NGU

Since gonorrhea and chlamydia are negative, consider these pathogens:

• Mycoplasma genitalium (responds better to azithromycin than doxycycline) 1
• Ureaplasma urealyticum (implicated in up to one-third of nonchlamydial NGU cases) 1
• Trichomonas vaginalis (reserve testing for nonresponsive cases or if contact history suggests this) 1
• HSV (Herpes Simplex Virus) (consider if severe dysuria with meatitis or visible genital lesions) 1

Specific diagnostic tests for Mycoplasma genitalium and Ureaplasma urealyticum are not routinely indicated because detection is difficult and would not alter initial therapy. 1 However, if symptoms persist after standard treatment, Mycoplasma genitalium testing is recommended. 2

Critical Management Steps

Partner Management

• Refer all sexual partners within the preceding 60 days for evaluation and treatment 1
• Partners should receive the same treatment regimen even if asymptomatic 1

Patient Instructions

• Abstain from sexual intercourse until 7 days after therapy is initiated AND symptoms have resolved AND partners have been adequately treated 1
• Return for evaluation if symptoms persist or recur after completing therapy 1

Follow-Up for Persistent or Recurrent Symptoms

If Symptoms Persist After Initial Treatment

Symptoms alone without documentation of urethral inflammation are NOT sufficient basis for re-treatment. 1 You must re-document urethritis using the same criteria above before prescribing additional antibiotics. 1

Consider These Causes for Treatment Failure

• Trichomonas vaginalis (perform wet mount or NAAT testing) 1
• HSV (examine for genital lesions; consider HSV testing if severe dysuria with meatitis) 1
• Mycoplasma genitalium (test specifically if available, as this organism may require different treatment) 1, 2
• Chronic prostatitis/chronic pelvic pain syndrome (if pain, discomfort, and irritative voiding symptoms persist beyond 3 months) 1

Additional Testing for Recurrent Cases

• Perform testing for other STDs including syphilis and HIV 1
• Consider urethral culture for Trichomonas vaginalis 1
• Consider HSV testing if genital lesions present 1

Common Pitfalls to Avoid

• Do not treat empirically without documenting urethritis unless the patient is high-risk and unlikely to return 1
• Do not assume treatment failure without re-documenting objective signs of urethritis 1
• Do not overlook partner treatment, as reinfection from untreated partners is a common cause of recurrent symptoms 1
• Do not miss alternative diagnoses like HSV or Trichomonas if the patient has contact history or suggestive symptoms 1